Molecular Modeling of the Fluorination Effect on the Penetration of Nanoparticles across Lipid Bilayers.

The fluorinated decorations have recently been widely used in many biomedical applications. However, the potential mechanism of the fluorination effect on the cellular delivery of nanoparticles (NPs) still remains elusive. In this work, we systemically explore the penetration of a perfluoro-octanethiol-coated gold NP (PF-Au NP) and, for comparison, an octanethiol-coated gold NP (OT-Au NP) across lipid bilayers. We also investigated the effect of these two types of NPs on the properties of lipid bilayers. Our findings indicate that the lipid type and the surface tension of the lipid bilayer significantly impact the penetration capabilities of the fluorinated gold NP. By examining the distribution of ligands on the surface of the two types of NPs in water and during the penetration process, we unveil their distinct penetration characteristics. Specifically, the PF-Au NP exhibits amphiphobic behavior (both hydrophobic and lipophobic), while the OT-Au NP exhibits solely hydrophobic characteristics. Finally, we observe that the penetration capabilities can be increased by adjusting the degree of fluorination of the ligands on the NP surface. Overall, this study provides useful physical insights into the unique properties of the fluorinated decorations in NP permeation.

Interaction of serum proteins with SARS-CoV-2 RBD.

The outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a worldwide public health crisis. When the SARS-CoV-2 enters the biological fluids in the human body, different types of biomolecules (in particular proteins) may adsorb on its surface and alter its infection ability. Although great efforts have recently been devoted to the interaction of specific antibodies with the SARS-CoV-2, it still remains largely unknown how the other serum proteins affect the infection of the SARS-CoV-2. In this work, we systematically investigate the interaction of serum proteins with the SARS-CoV-2 RBD by molecular docking and all-atom molecular dynamics simulations. It is found that non-specific immunoglobulins (Ig) indeed cannot effectively bind to the SARS-CoV-2 RBD while human serum albumin (HSA) may have some potential in blocking its infection (to ACE2). More importantly, we find that the RBD can cause significant structural changes in Apolipoprotein E (ApoE), by which SARS-CoV-2 may hijack the metabolic pathway of ApoE to facilitate its cell entry. The present study enhances the understanding of the role of protein corona in the bio-behaviors of SARS-CoV-2, which may aid the more precise and personalized treatment for COVID-19 infection in the clinic.

Improving the Performance of MM/PBSA in Protein-Protein Interactions via the Screening Electrostatic Energy.

Accurate calculation of protein-protein binding free energy is of great importance in biological and medical science, yet it remains a hugely challenging problem. In this work, we develop a new strategy in which a screened electrostatic energy (i.e., adding an exponential damping factor to the Coulombic interaction energy) is used within the framework of the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) method. Our results show that the Pearson correlation coefficient in the modified MM/PBSA is over 0.70, which is much better than that in the standard MM/PBSA, especially in the Amber14SB force field. In particular, the performance of the standard MM/PBSA is very poor in a system where the proteins carry like charges. Moreover, we also calculated the mean absolute error (MAE) between the calculated and experimental ΔG values and found that the MAE in the modified MM/PBSA was indeed much smaller than that in the standard MM/PBSA. Furthermore, the effect of the dielectric constant of the proteins and the salt conditions on the results was also investigated. The present study highlights the potential power of the modified MM/PBSA for accurately predicting the binding energy in highly charged biosystems.

Fabrication of Pascal-triangle Lattice of Proteins by Inducing Ligand Strategy.

A protein Pascal triangle has been constructed as new type of supramolecular architecture by using the inducing ligand strategy that we previously developed for protein assemblies. Although mathematical studies on this famous geometry have a long history, no work on such Pascal triangles fabricated from native proteins has been reported so far due to their structural complexity. In this work, by carefully tuning the specific interactions between the native protein building block WGA and the inducing ligand R-SL, a 2D Pascal-triangle lattice with three types of triangular voids has been assembled. Moreover, a 3D crystal structure was obtained based on the 2D Pascal triangles. The distinctive carbohydrate binding sites of WGA and the intralayer as well as interlayer dimerization of RhB was the key to facilitate nanofabrication in solution. This strategy may be applied to prepare and explore various sophisticated assemblies based on native proteins.

Controlling the Interaction of Nanoparticles with Cell Membranes by the Polymeric Tether.

The well control over the cell-nanoparticle interaction can be of great importance and necessity for different biomedical applications. In this work, we propose a new and simple way (i.e., polymeric tether) to tuning the interaction between nanoparticles and cell membranes by dissipative particle dynamics simulations. It is found that the linked nanoparticles (via polymeric tether) can show some cooperation during the cellular uptake and thereby have a higher wrapping degree than the single nanoparticle. The effect of the property of the polymer on the wrapping is also investigated, and it is found that the length, rigidity, and hydrophobicity of the polymer play an important role. More interestingly, the uptake of linked nanoparticles could be adjusted to the firm adhesion via two rigid polymeric tethers. The present study may provide some useful guidelines for novel design of functional nanomaterials in the experiments.